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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974-1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
No guideline study and non-GLP but performed according to scientific standards at time of performance. Acceptable based on nowadays existing guidlines and standards. Well performed and documented. Reliability declaration regarding procedures and performance available.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Two-generation study including a segment II phase for developmental toxicity
GLP compliance:
no
Remarks:
but reliability declaration from study director included
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hostapur SAS 60
- Physical state: aqueous slurry
- Analytical purity: 60%
- Composition of test material, percentage of components: 60% Hostapur SAS 93, water
- Isomers composition: n.a.
- Purity test date: 1974-09-01
- Lot/batch No.: NR T 2/112
- Expiration date of the lot/batch: 1979-10-01
- Radiochemical purity (if radiolabelling): n.a.
- Specific activity (if radiolabelling): n.a.
- Locations of the label (if radiolabelling): n.a.
- Expiration date of radiochemical substance (if radiolabelling): n.a.
- Stability under test conditions: stability and homogeneity guaranteed
- Storage condition of test material: in darkness at room temperature
- Other:

Test animals

Species:
rat
Strain:
other: CD
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K.
- Age at study initiation: (P) = weanling rats
- Weight at study initiation: (P) Males: 79 +/- 3g; (P) Females: 87 +/- 3 g
- Fasting period before study: no
- Housing: polypropylene cages
- Use of restrainers for preventing ingestion (if dermal): no
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 °C
- Humidity (%): 50 +/-20%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): Spratts Laboratory Diet No. 2
- Storage temperature of food: refrigerator


VEHICLE
- Justification for use and choice of vehicle (if other than water): n.a.
- Concentration in vehicle: n.a.
- Amount of vehicle (if gavage): n.a.
- Lot/batch no. (if required): n.a.
- Purity: n.a.
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: 60 days (three pregnancies derived from each of two generations)
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy
- After 5 days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: no
- After successful mating each pregnant female was caged separately
- Any other deviations from standard protocol: Approximately 20 days after weaning of the first (A) litters the females were re-mated with different males to produce the second (B) litters. This was repeated a second time to produce the third (C) litters.
Duration of treatment / exposure:
60 days prior to mating and throughout three successive pregnancies (fertility)
Gestation days 6 to 15 only for females during organogenesis stage (development)
Frequency of treatment:
daily
Duration of test:
gestation day 6 to 15.

For the P0 study:
F1 parental animals not mated until approximately 10 weeks after selected from the F1 litters.
- Selection of parents from F1 generation when pups were approximately 15 days of age.
- Age at mating of the mated animals in the study: approximately 13 weeks
Doses / concentrationsopen allclose all
Dose / conc.:
0 ppm
Remarks:
Remarks
Doses / Concentrations:
0, 1000, 3000, 10000 ppm
Basis:
nominal in diet
Developmental groups 5, 6, 7
Dose / conc.:
1 000 ppm
Dose / conc.:
3 000 ppm
Dose / conc.:
10 000 ppm
No. of animals per sex per dose:
25 per sex per group
Control animals:
yes
Details on study design:
- Dose selection rationale: Based on repeated-dose toxicity study and expert judgement
- Rationale for animal assignment (if not random): random
- Other: Intra-uterin development (segment II phase) investigated in groups from F1 and F2 generation

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


BODY WEIGHT: Yes
- Time schedule for examinations: weekly


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food intake per cage of five rats was recorded and the mean intake per rat calculated


OTHER: Heamtological investigations, absolute and relative organ weights, histopathological investigation of tissues
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other:
Fetal examinations:
- External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No data
Statistics:
Mann-Whitney non-parametric U test; chi-squared test incorporating Yates` correction
Indices:
Reproductive indices
Mean litter size, mean litter weight, mean offspring weight (day 1, 21, 25), mean offspring weight on
day 4 post partum

Offspring viability indices
Viability index, live birth index
Historical control data:
OTHER: Heamtological investigations, absolute and relative organ weights, histopathological
investigation of tissues

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Slight body weight gain depression in animals of the highest dose group (10000 ppm) (continously treated)

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOEL
Effect level:
>= 1 000 ppm (nominal)
Based on:
not specified
Basis for effect level:
other: see 'Remark'
Remarks on result:
other: Generation: P, F1a, F1b, F2a, F2b (migrated information)
Dose descriptor:
NOEL
Effect level:
>= 3 000 - <= 10 000 ppm (nominal)
Based on:
not specified
Basis for effect level:
other: See Remark
Remarks on result:
other:

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Changes in litter size and weights:
effects observed, non-treatment-related
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOEL
Effect level:
>= 10 000 ppm (nominal)
Sex:
not specified
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOEL
Effect level:
>= 10 000 ppm (nominal)
Sex:
not specified
Basis for effect level:
other: embryotoxicity

Fetal abnormalities

Key result
Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Treatment during organogenesis (gestation days 6 to 15) up to 10000 ppm gave no indication of embryotoxicity or teratogenicity (neither in F1-generation nor in F2-generation).
Executive summary:

Continous administration of sec-alkane sulfonate-sodium salts SAS to male and female rats at dietary concentrations of 1000 ppm, 3000 ppm or 10000 ppm was associated with a slight depression of bodyweight gain in male rats throughout the F0 and F1 generation. Treatment during organogenesis (gestation days 6 to 15) at dietary concentrations up to 10000 ppm gave no indication of teratogenic responses in either generation.